Efficacy of topical cyclosporine-loaded nanocapsules on keratoplasty rejection in the rat.
OBJECTIVE
To evaluate the efficacy of a topical formulation of nanocapsules loaded with 1% cyclosporine A (CsA), which has been previously demonstrated to enhance CsA corneal penetration, compared to 1% CsA in migliol oil on a penetrating keratoplasty rejection model in the rat.


METHODS
Lewis rats received orthotopic corneal allografts from inbred Fisher donors. Rats were treated with 10 microliters of the following topical solutions four times daily for 30 days, starting one day before surgery: Group 1 (n = 9), 1% CsA-loaded nanocapsules; group 2 (n = 13), 1% CsA dissolved in migliol oil; group 3 (n = 12), migliol oil; group 4 (n = 13), no treatment. Rejection index, mean survival time and rejection percentage were calculated for each group, and CsA levels in blood were measured.


RESULTS
The rejection percentage was 84.6% for group 2, 91.7% for group 3, and 100% for groups 1 and 4, with no significant differences among groups. Mean graft survival time was 7.3 days for group 1, 15.5 days for group 2, 8.36 days for group 3, and 7.69 days for group 4, with significant differences between group 2 and the other groups. Systemic CsA levels were only detectable in group 2.


CONCLUSIONS
CsA formulated in migliol oil delayed corneal rejection onset, but blood levels were evident in this group. CsA loaded-nanocapsules showed no effect on rejection and the drug was not detectable in blood. These data, along with the current concepts on corneal graft rejection immunology, suggest that the immunomodulatory effect of topical CsA in the prevention of corneal graft rejection may be systemically-mediated.
Juberías
J R
JR
Ocular Immunology Unit, Instituto Oftalmobiología Aplicada (IOBA), University of Valladolid, Spain.
Calonge
M
M
Gómez
S
S
López
M I
MI
Calvo
P
P
Herreras
J M
JM
Alonso
M J
MJ
D000287:Administration, Topical; D000818:Animals; D002214:Capsules; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005260:Female; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015948:Keratoplasty, Penetrating; D009821:Oils; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew
D002214:Capsules; D007166:Immunosuppressive Agents; D009821:Oils; D016572:Cyclosporine